Cognitive impairment and CSF proteome modification after oral bacteriotherapy in HIV patients

Abstract

Objective: To investigate whether a probiotic supplementation to cART patients modifies the cerebrospinal fluid (CSF) proteome and improves neurocognitive impairment. Methods: 26 CSF samples from 13 HIV-positive patients [six patients living with HIV (PLHIV) and seven patients with a history of AIDS (PHAIDS)] were analyzed. All patients underwent to neurocognitive evaluation and blood sampling at baseline and after 6 months of oral bacteriotherapy. Immune phenotyping and activation markers (CD38 and HLA-DR) were evaluated on peripheral blood mononuclear cells (PBMC). Plasma levels of IL-6, sCD14, and MIP-1β were detected, by enzyme-linked immunosorbent assay (ELISA). Functional proteomic analysis of CSF sample was conducted by two-dimensional electrophoresis; a multivariate analysis was performed by principal component analysis (PCA) and data were enriched by STRING software. Results: Oral bacteriotherapy leads to an improvement on several cognitive test and neurocognitive performance in both groups of HIV-positive subjects. A reduction in the percentage of CD4 + CD38 + HLA-DR + T cells was also observed at peripheral level after the probiotic intake (p = 0.008). In addition, the probiotic supplementation to cART significantly modifies protein species composition and abundance at the CSF level, especially those related to inflammation (β2-microglobulin p = 0.03; haptoglobin p = 0.06; albumin p = 0.003; hemoglobin p = 0.003; immunoglobulin heavy chains constant region p = 0.02, transthyretin p = 0.02) in PLHIV and PHAIDS. Conclusions: Our results suggest that oral bacteriotherapy as a supplement to cART could exert a role in the amelioration of inflammation state at peripheral and CNS level.

Nusinersen Modulates Proteomics Profiles of Cerebrospinal Fluid in Spinal Muscular Atrophy Type 1 Patients

“…In patients with stroke, TTR has been described as a positive prognostic indicator of clinical outcome [ 119 ]. Confirming this, dysregulations of TTR levels characterize several neurological disorders [ 120 , 121 , 122 , 123 , 124 , 125 ]. In particular, the mutant and wild type TTR amyloidoses are human disorders caused by TTR misfolding, native tetrameric structure lost, and insoluble aggregate formation and deposition in different organs [ 33 ].…”

“…CSF sample preparation was performed as previously described [ 123 ]. Briefly, 333 μL, 666 μL, and 3 mL of CSF were overnight precipitated in 1:4 cold acetone for each analytical and 2D western blot (wb) and Mass Spectrometry (MS)-preparative gels, respectively.…”

Hypothyroidism symptoms in LT4-euthyroid thyroidectomized patients reflect an alteration of the serum proteome

“…Therefore, altered coagulation processes and complement system activation that we found, could suggest the presence of a potential vascular in ammation in FT3 "reduced" patients as already reported in subclinical hypothyroidism 16 . Of interest, different studies associate higher serum levels of in ammatory molecules to the fatigue and migraine onset, a characteristic symptoms of hypothyroidism [17][18][19] as well as to depression 20 . Indeed, in ammation related to a potential endothelial dysfunction, as suggested by our data, was already reported in depression 21 and may prove to be the cause for this illness also in FT3 reduced patients.…”

Targeting Microbiome: An Alternative Strategy for Fighting SARS-CoV-2 Infection

“…Probiotics may play a beneficial role even though there is much to be discovered on their specific mechanisms of action against SARS-CoV-2. The damage of the gut barrier integrity associated with microbial translocation along with the dysregulated inflammatory response explains why probiotics could represent a valuable therapeutic tool in COVID-19 patients [56,69,[75][76][77][78][79].…”